Muscadine Grape Skin Extract Inhibits Prostate Cancer Cells by Inducing Cell-cycle Arrest, and Decreasing Migration Through Heat Shock Protein 40
Overview
Authors
Affiliations
Previously we demonstrated that muscadine grape skin extract (MSKE), a natural product, significantly inhibited androgen-responsive prostate cancer cell growth by inducing apoptosis through the targeting of survival pathways. However, the therapeutic effect of MSKE on more aggressive androgen-independent prostate cancer remains unknown. This study examined the effects of MSKE treatment in metastatic prostate cancer using complementary PC-3 cells and xenograft model. MSKE significantly inhibited PC-3 human prostate cancer cell tumor growth and . The growth-inhibitory effect of MSKE appeared to be through the induction of cell-cycle arrest. This induction was accompanied by a reduction in the protein expression of Hsp40 and cell-cycle regulation proteins, cyclin D1 and NF-kBp65. In addition, MSKE induced p21 expression independent of wild-type p53 induced protein expression. Moreover, we demonstrate that MSKE significantly inhibited cell migration in PC-3 prostate cancer cells. Overall, these results demonstrate that MSKE inhibits prostate tumor growth and migration, and induces cell-cycle arrest by targeting Hsp40 and proteins involved in cell-cycle regulation and proliferation. This suggests that MSKE may also be explored either as a neo-adjuvant or therapeutic for castration resistant prostate cancer.
Huff M, Hulse-Kemp A, Scheffler B, Youngblood R, Simpson S, Babiker E BMC Genomics. 2023; 24(1):409.
PMID: 37474911 PMC: 10357881. DOI: 10.1186/s12864-023-09514-y.
Klepin H, Tooze J, Bitting R, Davis B, Pleasant K, Melo A J Geriatr Oncol. 2023; 14(4):101478.
PMID: 36990930 PMC: 10164712. DOI: 10.1016/j.jgo.2023.101478.
Heat Shock Proteins in Benign Prostatic Hyperplasia and Prostate Cancer.
Ratajczak W, Lubkowski M, Lubkowska A Int J Mol Sci. 2022; 23(2).
PMID: 35055079 PMC: 8779911. DOI: 10.3390/ijms23020897.
Scaria B, Sood S, Raad C, Khanafer J, Jayachandiran R, Pupulin A Int J Mol Sci. 2020; 21(22).
PMID: 33187200 PMC: 7697102. DOI: 10.3390/ijms21228480.
Joshi T, Patel I, Kumar A, Donovan V, Levenson A Mol Nutr Food Res. 2020; 64(16):e2000326.
PMID: 32618118 PMC: 8103660. DOI: 10.1002/mnfr.202000326.